发热伴血小板减少综合征患者外周血浆细胞免疫表型特征及临床意义
Immunophenotypic characteristics and clinical significance of plasma cells in peripheral blood of patients diagnosed as severe fever with thrombocytopenia syndrome
摘要目的:分析发热伴血小板减少综合征(SFTS)患者外周血浆细胞免疫表型特征,探讨其在SFTS中的变化及临床意义。方法:回顾性病例对照研究。收集大连医科大学附属第二医院2022年8月1日至2024年7月30日确诊的SFTS患者17例(SFTS组),包括男7例,女10例,年龄67(58,72)岁,以同期健康管理中心15名健康人作为对照组。SFTS组根据住院期间临床结局进一步分为存活亚组(12例)和死亡亚组(5例)。采用流式细胞术检测外周血浆细胞数量、CD抗原标志及胞浆内免疫球蛋白轻链(cκ和cλ)表达。采用Spearman相关性分析浆细胞免疫表型与实验室检测指标的相关性,受试者工作特征(ROC)曲线分析浆细胞免疫表型特征对SFTS预后的预测价值。结果:SFTS组浆细胞比例为4.10%(2.81%,5.30%),明显高于对照组的0.01%(0.01%,0.01%),差异有统计学意义( Z=4.985, P<0.001)。SFTS组浆细胞CD19、CD20、CD45、CD56抗原表达率分别为100%、0、100%、0;cκ型轻链比例为9.30%(2.95%,12.65%),cλ型轻链比例为89.30%(85.60%,94.85%),cκ/cλ型轻链比值0.10(0.03,0.15)。死亡亚组浆细胞、cλ型轻链比例高于存活亚组,而cκ型轻链比例、cκ/cλ型轻链比值低于存活亚组,差异均有统计学意义( P均<0.05)。SFTS患者浆细胞比例、cλ型轻链比例与活化部分凝血酶时间(APTT)、凝血酶时间(TT)及D-二聚体水平呈正相关( r=0.498~0.674, P均<0.05),与血小板数量呈负相关( r=-0.668、-0.588, P均<0.05),cκ型轻链比例、cκ/cλ型轻链比值与血小板数量呈正相关( r=0.640、0.631, P<0.05),与乳酸脱氢酶、APTT、TT及D-二聚体水平呈负相关( r=-0.708~-0.520, P均<0.05)。浆细胞、cκ型轻链、cλ型轻链比例及cκ/cλ型轻链比值预测SFTS患者死亡的曲线下面积分别为1.000、0.967、0.900、0.967。 结论:SFTS患者外周血出现浆细胞扩增的现象,其免疫表型特征为CD19 +CD20 -CD45 +CD56 -,系λ型轻链单克隆细胞群。外周血浆细胞免疫表型改变与SFTS疾病严重程度和预后相关。
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abstractsObjective:To analyze the immunophenotypic characteristics of plasma cells in the peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS) and to explore their clinical significance.Methods:It was a retrospective case-control study. A total of 17 SFTS patients who were hospitalized in the Second Affiliated Hospital of Dalian Medical University from 1 August 2022 to 30 July 2024 were enrolled as SFTS group, including 7 males and 10 females, aged 67 (58, 72) years old. Besides, 15 healthy individuals from the Health Management Center were selected as the control group. The SFTS patients were further divided into survival group ( n=12) and non-survival group ( n=5). Flow cytometric analysis was used to detect the proportion of plasma cells and assess the expression of CD antigen markers and cytoplasmic immunoglobulin light chains (cκand cλ). Spearman correlation analysis was used to analyze the correlation between plasma cell immunophenotypes and laboratory test indicators. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of plasma cells in the prognosis of SFTS. Results:Compared with the control group, the SFTS group exhibited a significant increase in the proportions of plasma cells [4.10% (2.81%, 5.30%) vs 0.01% (0.01%, 0.01%), P<0.05]. In the SFTS group, the expression rate of CD19, CD20, CD45, and CD56 antigens on plasma cells was 100%, 0, 100%, and 0, respectively, the proportion of cκ light chains was 9.30% (2.95%, 12.65%), and the proportion of cλ light chains was 89.30% (85.60%, 94.85%), with a cκ/cλ light chain ratio of 0.10 (0.03, 0.15). The proportion of plasma cells and cλ light chains was significantly higher in the non-survival group than in the survival group, while the proportion of cκ light chains and cκ/cλ light chains ratio were lower in the non-survival group compared to the survival group (all P<0.05). The proportion of plasma cells and cλ light chains were positively correlated with activated partial thromboplastin time (APTT), thrombin time (TT), and D-dimer levels ( r=0.498-0.674, all P<0.05), while negatively correlated with platelet count ( r=-0.668, -0.588, both P<0.05). Moreover, the proportion of cκ light chains and cκ/cλ light chains ratio were positively correlated with platelet count ( r=0.640, 0.631, both P<0.05), while negatively correlated with lactate dehydrogenase, APTT, TT, and D-dimer levels ( r=-0.708--0.520, all P<0.05). The area under the curve of the proportion of plasma cells, cκ light chains, cλ light chains and cκ/cλ light chains ratio to predict mortality of SFTS was 1.000, 0.967, 0.900 and 0.967, respectively. Conclusions:SFTS patients exhibit an expansion of plasma cells in peripheral blood, characterized by the immunophenotype CD19 +CD20 -CD45 +CD56 -, which is considered as a λ type light chain monoclonal cell subset. The immunophenotypic alterations of plasma cells in peripheral blood are associated with the severity and prognosis of SFTS patients.
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